Description:
The purpose of this study is to determine the safety of a cell therapy, T-allo10, after
αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the
patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD).
The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D)
administered after infusion of αβdepleted-HSCT in children and young adults with hematologic
malignancies.
A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10
cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of
T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore
improvements in immune reconstitution.
All participants on this study must be enrolled on another study: NCT04249830
Title
- Brief Title: Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback
- Official Title: Phase 1/1b Study of T-allo10 Infusion After HLA-Partially Matched Related or Unrelated TCR αβ+ T-cell/ CD19+ B-cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (αβ Depleted-HSCT) in Children and Young Adults Affected by Hematologic Malignancies
Clinical Trial IDs
- ORG STUDY ID:
IRB-58549
- SECONDARY ID:
BMT 367 - T-allo10 Alpha Beta
- NCT ID:
NCT04640987
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Allogeneic Stem Cell Transplant | | Experimental: Stem Cell Transplant |
T-allo10 cells addback | | Experimental: Stem Cell Transplant |
Purpose
The purpose of this study is to determine the safety of a cell therapy, T-allo10, after
αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the
patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD).
The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D)
administered after infusion of αβdepleted-HSCT in children and young adults with hematologic
malignancies.
A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10
cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of
T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore
improvements in immune reconstitution.
All participants on this study must be enrolled on another study: NCT04249830
Trial Arms
Name | Type | Description | Interventions |
---|
Experimental: Stem Cell Transplant | Experimental | The participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years. | - Allogeneic Stem Cell Transplant
- T-allo10 cells addback
|
Eligibility Criteria
Inclusion Criteria prior to enrollment:
- 1. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.
- 2. Patients deemed eligible for allogeneic HSCT under the originating study, NCT
04249830
- 3. Patients with life-threatening hematological malignancies for which HSCT has been
recommended:
1. High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
2. High-risk AML in 1st CR, AML in 2nd or subsequent CR;
3. Myelodysplastic syndrome;
4. JMML (Juvenile myelomonocytic leukemia);
5. Non-Hodgkin lymphomas in 2nd or subsequent CR;
6. Other hematologic malignancies eligible for stem cell transplantation per
institutional standard.
- 4. All subjects ≥ 18 years of age must be able to give informed consent, or adults
lacking capacity to consent must have a LAR available to provide consent. For subjects
<18 years old their LAR (i.e. parent or guardian) must give informed consent.
Pediatric subjects will be included in age appropriate discussion and verbal assent
will be obtained for those > 7 years of age, when appropriate.
Inclusion criteria prior to T-allo10 infusion:
1. Patient already received αβdepleted-HSCT and has myeloid engraftment.
2. Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of
grade III/IVaGvHD.
Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:
1. Not eligible to receive HSCT on NCT04249830
2. Received another investigational agent within 30 days of enrollment.
3. Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
4. Patient or donor is not willing or able to undergo an additional non-mobilized
apheresis for collection of MNC prior to donation of cells for participation in
NCT04249830.
Maximum Eligible Age: | 45 Years |
Minimum Eligible Age: | 1 Month |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with myeloid engraftment after T-allo10 |
Time Frame: | Through day 35 (+/- 7 days) after αβdepleted-HSCT |
Safety Issue: | |
Description: | IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60(+/-10days). |
Secondary Outcome Measures
Measure: | Number of participants with ≥grade 3 adverse event related to T-allo10 infusion |
Time Frame: | Through 1 year after αβdepleted-HSCT |
Safety Issue: | |
Description: | |
Measure: | Number of participants with grade II-IV aGvHD |
Time Frame: | Assessed at day 90 after αβdepleted-HSCT |
Safety Issue: | |
Description: | |
Measure: | Number of participants with grade III-IV aGvHD |
Time Frame: | Assessed at day 180 after αβdepleted-HSCT |
Safety Issue: | |
Description: | |
Measure: | Number of participants with cGvHD |
Time Frame: | Assessed at 1 year after αβdepleted-HSCT |
Safety Issue: | |
Description: | |
Measure: | Leukemia-free survival |
Time Frame: | Assessed at 1 year after αβdepleted-HSCT |
Safety Issue: | |
Description: | Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause. |
Measure: | Number of participants with disease relapse |
Time Frame: | Assessed at 1 year after αβdepleted-HSCT |
Safety Issue: | |
Description: | Disease relapse is defined as the return of signs and symptoms of a disease after a remission. |
Measure: | Non-relapse mortality |
Time Frame: | Assessed at Day 90 after αβdepleted-HSCT |
Safety Issue: | |
Description: | |
Measure: | Non-relapse mortality |
Time Frame: | Assessed at 1 year after αβdepleted-HSCT |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Stanford University |
Last Updated
July 19, 2021